Targeted delivery of cells, such as the targeting of therapeutic cells to the endothelium of dysfunctional tissues, remains a formidable challenge. Systemic delivery of therapeutic cells can be accomplished through the circulatory system. Luminal endothelial cells (ECs) form a natural barrier between the blood and surrounding tissue. Under steady-state physiological conditions, luminal ECs are mostly quiescent and form a tight and impermeable barrier. During various pathological processes, such as tissue injury, inflammation, atherosclerosis and tumor, soluble factors such as, SDF-1α, TGF-β, and IL-1, are released into tissue, and the endothelium is stimulated by these factors and switch to a highly permeable status wherein circulating cells, including bone marrow-derived endothelial progenitor cells (EPC), mesenchymal stem cells (MSC) as well as inflammatory cells (IC), are able to infiltrate into the pathologically disrupted tissues. However, infiltration of cells into disordered tissues is not a passive process.
Recruitment of circulating cells into a tissue involves an active and well-modulated circulating cell for EC interaction, and subsequent circulating cell transendothelial migration. Upregulated E-selectin on luminal EC at injured or tumor tissue is believed to be responsible for mediating EPC homing. (Oh, I. Y. et al., Blood 110, 3891-3899 (2007); Liu, Z. J. et al., Ann Surg 252, 625-634 (2010); Liu, Z. J. et al., Ann. Surg. 254, 450-456; discussion 456-457 (2011)). When EPC circulate through the disrupted tissues, the EPC adhere to the E-selectin on the EC surface of capillaries, a process that is followed by subsequent transendothelial migration and extravasation of the EPC. In this sequence of events, adhesion molecule pairs expressed on luminal EC and circulating cells, such as E-selectin and E-selectin ligands, play a pivotal role in directing the selective and specific homing of circulating cells to damaged tissues.
An appropriate adhesion molecule can be utilized to direct cell homing to where a corresponding binding partner is highly or selectively expressed on the luminal EC within the targeted tissue. Thus, by attaching the proper adhesion molecule(s) on the surface of a cell, such as a therapeutic stem or progenitor cells being used for cell-based regenerative medicine therapies, the cell can be directed to a tissue of interest. However, attaching one or more proper adhesion molecule(s) on the cell surface via a biological approach, such as gene expression, has notable disadvantages, as gene expression may bring about downstream secondary effects that can raise safety concerns or lead to unwanted side-effects. For instance, certain highly or newly expressed molecule(s) or even some non-coding sequences in vectors utilized for gene expression manipulation, may affect cell differentiation, which raises the concern for the ultimate fate of the stem or progenitor cells being used for cell-based regenerative medicine therapies.
Accordingly, there is a need for compositions and methods for targeting a cell to a tissue. The present invention meets this need and provides related advantages.